In vertebrate embryonic development, the segmentation clock controls the cyclic formation of somites through presomitic mesoderm (PSM) cells. Somites are paired segmented structures along the anterior-posterior axis that eventually develop into vertebrae and ribs. Disruptions in the segmentation clock leads to defects in somitogenesis, resulting in congenital spinal diseases. The major patterning modules that are involved in segmentation clock is the clock and wavefront, which primarily relies on signaling gradients and cyclic oscillation. Mesodermal differentiation is regulated by combinatorial gradient system that involves the activity of the fibroblast growth factor (FGF), the Wnt/β-catenin, and the retinoic acid (RA) signaling pathways. The antagonistic gradients of these signals set a position of the determination front. In the tail bud and posterior mesoderm, FGF and Wnt signaling prevent cell maturation and the molecular oscillators start to express. The molecular oscillators rely on negative feedback loops to maintain their oscillatory expression patterns. As the cells move anteriorly, FGF signaling gradually decays and RA signaling began to strengthen. Meanwhile, the molecular oscillators propagate anteriorly with wave pattern. At the determination front, low levels of FGF signaling and high levels of RA signaling eliminate differentiation inhibition and initiate molecular oscillators to activate cyclic genes, such as Mesp2, leading to the formation of repetitive structures in somites. Advancements in live reporter and 2D culture systems have revealed that coupling delays in cell communication can maintain the synchronous segmentation clock between adjacent cells. Studies have shown that these coupling delays are controlled by Lfng gene, it can adjust coupling delays to fit in-phase oscillations by increasing the time required for intercellular DLL1-Notch signaling. To sum up, the dual homeostasis of opposing signaling gradients determines the segment boundaries, the distance traveled by a molecular oscillator in one oscillation cycle determines the somite size, and the delayed coupling in intercellular signaling regulates the synchronization of clock oscillations. These three factors interact with each other to form a segmentation clock network coordinating somitogenesis. Recent studies have revealed that the intercellular coupling delay mechanism is a major factor influencing the maintenance of oscillation synchronization. Intercellular coupling delay errors, such as increased or decreased delay time, can desynchronizing intercellular oscillations and resulting in somite fusion. However, the mechanisms governing how intercellular communication becomes involved in oscillation synchronization remains unclear. Congenital scoliosis (CS) is a result of anomalous development of the vertebrate which associate with somitogenesis malformation. We observed that deficiency or overdose of vitamin A intake in gestation may lead to CS. While the deep mechanism of how RA signaling regulates oscillation synchronization still need to be detected. With the rapid development of 3D culture systems, researchers have successfully recapitulated the formation of somite-like structures with antero-posterior identity and indicated that the rate of metabolism is directly proportional to that of development. In summary, deconstructing the segmentation clock in vitro facilitates the dissection of regulation networks of the segmentation clock and offers an excellent proxy for studying the metabolic regulation of somitogenesis speed across species and the mechanisms underlying the formation of bilateral symmetry. It also creates a platform for exploring dysregulation mechanisms involved in the development of pathological somite defects.

Objective To evaluate the prognostic value of the model for end-stage liver disease (MELD) and △MELD in liver failure patients infected with hepatitis B virus.Methods Based on prospective study design,98 hospitalized cases were studied and followed up for 24 weeks.The clinical data were recorded.We calculated the score of MELD and △MELD,and also compare the score between the survival group and death group.Using ROC curve plotting obtained the better decisive threshold.The case fatality rate were compared at different time points which the patients were classified by the best critical value of MELD and △MELD.We draw the Kaplan-Meier survival curve of different group and analyse the change of survival rate by log-rank analysis.Results 52 of 97 patients died and 46 survive during 24 weeks of followup.There was significant difference between the two groups for MELD and △MELD (P ＜ 0.01 ).The case fatality rate in group which MELD ≥ 23 was obviously higher than in that MELD ＜ 23. The rate in group which △MELD ＞4.5 was obviously higher than in that △MELD ＜ 4.5 (P ＜ 0.001 ).The area under curve (AUC) for the twelfth and 24th week' s prognosis judgment of △MELD(0.823,0.815) was larger than that of MELD ( 0.680,0.684 ) ( P ＜ 0.05 ).Survival analyses (Kaplan-Meier) indicated that there were significant differences in cumulative survival rates among the groups which were grouped by optimization critical value(P =0.000).Conclusions The scoring system of MELD also applied to the forecasting of prognosis for severe hepatitis B patients in China.The accuracy of △MELD to predict the prognosis was higher than that of MELD.The combination of MELD and △MELD showed good clinical practical value.

OBJECTIVETo summarize the anesthetic management in fetal lamb cardiac bypass.

METHODSFive ewes at 120-140 days of gestation were anesthetized intramuscularly with katamine hydrochloride, intubated and ventilated with a respirator. Anesthesia was maintained with fentanyl and vecuronium. Lactated Ringer's solution and magnesium sulfate were infused to maintain the mean blood pressure (MAP) over 70 mmHg and uterine relaxation. The fetal lambs received anesthesia with fentanyl and vecuronium intramuscularly via the uterine wall. Fetal cardiac bypass was established with pulmonary artery and right atrium cannulation, lasting for 30 min. The hemodynamic and blood gas data of the ewes and fetal lambs were recorded before bypass, at 30 min during bypass, and at 1 and 2 h after cessation of bypass. The pulse index of the umbilical artery (PIua) and the ewe's uterine artery (PIeu) were monitored simultaneously.

RESULTSThe MAP and heart rate (HR) of the fetus remained normal during the anesthesia. PIua increased significantly after cessation of bypass (P<0.05). Although the fetal oxygen tension in the axillary artery remained normal, the fetal lambs showed hypercarbia and acidosis after cessation of bypass (P<0.05). The maternal MAP and HR remained normal. The PIeu decreased significantly during bypass (P<0.05) and recovered the normal level after cessation of bypass. The arterial blood gas of the ewes was normal during the experiment.

CONCLUSIONMaintaining high hemodynamics in the ewes, application of uterine relaxation and intensive care during anesthesia are crucial in anesthetic management of cardiac bypass in fetal lambs.

Anesthetics, Dissociative ; Animals ; Cardiopulmonary Bypass ; methods ; Female ; Fentanyl ; administration & dosage ; Fetal Heart ; surgery ; Goats ; surgery ; Ketamine ; administration & dosage ; Pregnancy ; Vecuronium Bromide ; administration & dosage